The overall goal of these studies is to better understand factor that cause overeating-driven metabolic disease. We are using skeletal muscle, primary site of nutrient deposal, to address the role of protein that coat the myocellular fat depot (the perilipins) play in regulating the fat they enclose and how this regulation fat influences susceptibility to metabolic disease. We hypothesis: perilipin 5 forms the myocellular fat storage organelle; only fat in this organelle is under appropriate myocellular regulation; and perilipin 5 levels determine the fat storage capacity of organelle and the overflow this organelle cause metabolically disruptive lipid to leak in the cytosol. Thus, we predict that increasing perilipin 5 levels will increase resistant to metabolic challenges. We will determine: the effects of perilipins on cellular fat packaging and release; what lipid intermediates and key metabolic proteins perilipin 5 recruits fat droplets to regulate fat flux; and affect of muscle-specific overexpression and ablation of perilipin 5 on lipid metabolism, insulin sensitivity and levels of metabolically disruptive lipid.